The long-term goal of this investigation is to clarify the role of dopamine in drug-induced tardive dyskinesias with particular reference to oral-facial dyskinesia (OFD). The first major objective will be to characterize the role of extrapyramidal structures, in this case the substantia nigra (SN), on supraspinal motor areas, in this case hypoglossal (XII) motoneurons. Cortical input from the tongue area of the motor cortex to XII motoneurons will be determined by intracellular recordings from XII motoneurons. The effect of the SN on the cortical-evoked activity in XII motoneurons will be determined by measuring alterations in cortical evoked activity following conditioning stimulation of the SN. Similar conditioning-test experiments will characterize SN modification of cortical-evoked extracellularly recorded activity of neurons in the spinal trigeminal nucleus which are believed to be a link in the cortical-hypoglossal pathway. The second major objective will be to determine whether the effects of the acute administration of neuroleptics such as chlorpromazine and haloperidol on SN-induced alterations in cortical-evoked activity of XII or SPV neurons are different from the effects of chronic administration of these same drugs. If the hypothesis of neuroleptic-induced dopamine receptor hypersensitivity is true, a marked difference is expected. The same techniques will be employed for this study as indicated above. In addition, putative neurotransmitters, their agonists and antagonists will be applied to single units of XII and SPV neurons in control, acute and chronic neuroleptic-treated animals. The third major objective will be to determine whether a dopaminergic-cholinergic counter-balancing system can be demonstrated at the single unit level by using intracellular, and extracellular recording techniques and iontophoretic administration of drugs in contol, acute and chronic neuroleptic- and deanol-treated animals.